Diseases in which neoplastic proliferation of plasma cells occurs are diseases in which plasma cells present in bone marrow become cancerous and proliferate into monoclonal cells. In the case of multiple myeloma that is a typical example of such diseases, abnormal plasma cells (myeloma cells) spread in bone marrow all over the body, and proliferate all over bone marrow in the whole body. The proliferation of the abnormal plasma cells (myeloma cells) causes various symptoms such as destruction of bone. The myeloma cells produce M protein, which is an abnormal immunoglobulin, and the M protein concentration rises in blood, whereby blood becomes viscous. M protein does not function as a proper antibody to recognize foreign substances, such as a pathogen that invades the body, and thus also causes decrease of immunity. These factors affect many organs and various signs occur. Typical signs are pain and damage of bone, hypercalcemia, renal damage, renal failure, anemia, etc.
Multiple myeloma occupies about 1% of all the cancers and occupies a little more than 10% of all the hematological malignant tumors. Thus, an effective therapeutic agent therefor is called for. At present, chemotherapies, such as combined use of merphalan and prednisone and use of thalidomide, and hematopoietic stem cell transplantation are mainly performed as therapy for multiple myeloma. However, in most cases, myeloma cells acquire resistance to these chemotherapeutic agents soon. Thus, in the existing therapeutic approach, the average survival time after development of symptoms is about three to five years, and the prognoses of myeloma patients are actually severe. Since these therapeutic agents do not act specifically on only target tumor cells, they exhibit toxicity also to normal cells and there is a problem that serious side effects are produced as a result.
One of the reasons why diseases in which neoplastic proliferation of plasma cells occurs, such as multiple myeloma, are very intractable is thought to be that myeloma stem cells, which are precursors of myeloma plasma cells, are not eliminated by therapy (Non-Patent Literature 1 and Non-Patent Literature 2). Since myeloma stem cells are present in a CD19+ cell fraction, therapy for multiple myeloma using an antibody (rituximab) to CD20 highly-expressed in the same pattern as CD19 has been attempted, but there has been no report that a sufficient therapeutic efficacy is obtained (Non-Patent Literature 3). In addition, development of therapy for multiple myeloma using an antibody has been attempted. For example, it is thought that IL-6 is a major proliferator for multiple myeloma cells (Non-Patent Literature 4 and Non-Patent Literature 5), and development of a therapeutic agent for multiple myeloma using a neutralizing antibody to IL-6 or an IL-6 receptor was attempted for the purpose of preventing an IL-6 signal transduction system. However, although proliferation inhibition of myeloma cells was observed in patients with plasma cell leukemia, tumors recurred and clinical efficacy has not been obtained (Non-Patent Literature 6 and Non-Patent Literature 7). Further, there have been reports that some antigen molecules (e.g., CD19 (Non-Patent Literature 8), CD20 (Non-Patent Literature 9), CD38 (Non-Patent Literature 10), CD54 (Non-Patent Literature 11), CD138 (Non-Patent Literature 12), Muc-1 (Non-Patent Literature 13), etc.) can be effective targets in antibody therapy, but a practical therapeutic agent has not been developed.